硫化氢对需氧菌性阴道炎相关病原体介导阴道炎症反应的作用

Effect of hydrogen sulfide on inflammatory response in vagina induced by aerobic vaginitis-related pathogens

目的探讨硫化氢(H_(2)S)对需氧菌性阴道炎的作用及其分子机制。方法使用大肠埃希菌(E.coli)和金黄色葡萄球菌(S.aureus)感染分别制备细胞(VK2/E6E7)和大鼠需氧菌性阴道炎模型。硫氢化钠(NaHS)被用为H_(2)S供体。采用CCK-8、蛋白印迹、qPCR和流式细胞术等分别检测细胞活性、蛋白表达、mRNA表达和细胞内氯离子水平。结果E.coli和S.aureus感染促进VK2/E6E7细胞和阴道组织中IL-6和IL-1β的生成,NaHS能显著抑制这些促炎细胞因子的产生。NaHS显著抑制E.coli或S.aureus感染引起的NF-κB(p65)磷酸化。NaHS显著降低E.coli和S.aureus感染阴道上皮细胞内的氯离子浓度。结论H_(2)S可能通过降低细胞内氯离子浓度而抑制NF-κB信号通路的激活,从而抑制E.coli和S.aureus感染引起的阴道炎症反应。H_(2)S可开发成为治疗需氧菌性阴道炎的潜在药物。

Objective To investigate the effect and molecular mechanism of hydrogen sulfide(H_(2)S)on inflammatory responses in aerobic vaginitis(AV).Methods Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)were used to establish cellular and rat AV models.Sodium hydrosulfide hydrate(NaHS)was used as an H_(2)S donor.CCK-8,western blot,qPCR,and flow cytometry were employed to detemine cell viability,protein and mRNA expression,and intracellular Cl-concentration,respectively.Results Both E.coli and S.aureus infection significantly promoted the production of IL-6 and IL-1βin VK2/E6E7 cells and vaginal tissues,whereas NaHS treatment reduced the production of these proinflammatory cytokines in AV cells and vaginal tissues.NaHS treatment significantly reduced phosphorylated NF-κB(p65)induced by E.coli or S.aureus infection.Furthermore,NaHS treatment inhibited E.coli-and S.aureus-induced intracellular Cl-accumulation in vaginal epithelial cells.Conclusion H_(2)S can inducing vaginal inflammatory responses in AV induced by E.coli and S.aureus infection,at least partially inducing intracellular Cl-accumulation and inhibiting the NF-κB signal pathway.H_(2)S might serve as a potential drug for treating AV.